Effects Of Astrocyte Activation In The Early Stage On The Aβ-induced Neuropathology In An Animal Model Of Alzheimer’s Disease

Alzheimer’s disease(AD)is the most common neurodegenerative disease.Amyloid precursor protein(APP)and its proteolytic product Aβ are key players in AD pathogenesis.AD is also closely associated with neuroinflammation responses in which astrocytes are deeply involved.However,the roles of astrocytes in AD remain elusive.In the present study,we crossed AD mouse model hAPP-J20 mice with GFAP-HSV-TK mice.GCV treatment in these mice induced increased expression of GFAP in the cortex between 3-5 months,indicating astrocytes were activated.Microglia and mature neurons,however,were spared in this treatment.Subsequently,we found that activation of astrocytes resulted in decreased amyloid plaque load in hAPP-J20 mice and recovered Calbindin and c-Fos expression in hippocampus.Western blotting analysis revealed that AQP4 expression was increased after activation of astrocytes,which may account partially for the reduced amyloid deposition in hAPP-J20 mice.Our data showed that early activation of astrocytes affected some of the neuropathologies in AD mice,the underlying mechanisms were warranted to be further investigated.